Areas of Research

Graduate Program Affiliations

Molecular Mechanisms of Neurodegeneration and Transporters

Professor, Department of Neurology and Neuroscience, is a neurologist/neurobiologist with a major commitment to investigations of the biology of glutamate transporters and their role in acute and chronic neurodegeneration. A primary focus of his laboratory is understanding the basic regulation of astroglial and neuronal glutamate transporters, and how dysregulation of these proteins- or their associated regulatory proteins, could contribute to neurological disorders such as amyotrophic lateral sclerosis, spinocerebellar ataxia and other neurodegenerative conditions. The lab is especially focused on regulation of glutamate transporter by drugs acting to activate transporter transcription, cytoplasmic and membrane interacting proteins which regulate the processing of transporter subtypes. The group has cloned and characterized three such proteins (GTRAPs- including beta III spectrin, PDZ RhoGEF, GTRAP3-18). Members of the lab focus on the role of transporter interacting proteins to modulate surface trafficking and cellular processing of transporters. Lab members have cloned several transporter promoters and is using these reagents to discover promoter activating pharmaceuticals. As a component of many of these studies the lab has generated BAC transgenic mice expressing promoter reporters for each of the glutamate transporters- GLT1, EAAT4 and GLAST. The also study the deregulation of glutamate transporter synthesis and metabolism in ALS.

Other projects in the laboratory focus on the biology of glutamate transport function and regulation: identification of neuronal factors and growth factors that regulate the normal expression of transporter subtypes, the role of EAAC1 in epilepsy, trafficking and pathobiology of truncated astroglial glutamate transporters, interacting proteins for the astroglial glutamate transporters. His lab uses high and low thruput systems and chemical libraries to identify drugs that activate EAAT genes for therapeutics. Studies on transgenic models of ALS include: neuroprotective studies using viral vector delivery approaches, neuroprotectant discovery, glial progenitor as neuroprotectants and neural and astroglial stem cell therapies in ALS -relevant models.